title: Continuous binding of the PAF molecule to its receptor is necessary for the long-term aggregation of platelets.
abstract: Human and rabbit platelets fully aggregated by platelet-activating factor (PAF) underwent slow disaggregation but were rapidly disaggregated by the PAF receptor antagonists WEB-2086, Y-24180, SM-12502, and CV-3988. Whereas the 1-alkyl-2-[3H]acetyl-sn-glycero-3-phosphocholine ([3H]acetyl-PAF) specifically bound to platelet receptors underwent slow and spontaneous dissociation, it dissociated promptly from its receptor when WEB-2086 was added, in parallel with platelet disaggregation and disappearance of P-selectin on the cell surface. Extracellular [3H]acetyl-PAF was rapidly deacetylated by normal rabbit platelets; some of the [3H]acetyl-PAF was bound to the cells and a very small amount of [3H]acetate was detected in the cells. In contrast, when 1-[3H]alkyl-2-acetyl-sn-glycero-3-phosphocholine was added to the platelets, the radioactivity was rapidly incorporated into the 1-alkyl-2-acyl-sn-glycero-3-phosphocholine fraction. These results indicate that 1) continuous binding of PAF to its receptor is necessary for prolonged platelet aggregation, which may be mediated through an unknown signaling system for a long-term cell response rather than a transient signaling system, and 2) most of the [3H]acetyl-PAF bound to platelets is metabolized extracellularly by ecto-type PAF acetylhydrolase, with the lyso-PAF generated being incorporated rapidly into the cells and converted to 1-alkyl-2-acyl-sn-glycero-3-phosphocholine.
authors.affiliation: Department of Pharmaco-Biochemistry, School of Pharmaceutical Science, University of Shizuoka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
authors.forename: J
authors.initials: J
authors.lastname: Sugatani
authors.forename: M
authors.initials: M
authors.lastname: Ino
authors.forename: M
authors.initials: M
authors.lastname: Shimura
authors.forename: M
authors.initials: M
authors.lastname: Akiyama
authors.forename: R
authors.initials: R
authors.lastname: Yamazaki
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: M
authors.initials: M
authors.lastname: Miwa
mesh_terms: D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D019007:P-Selectin / Q000096:biosynthesis / Q000097:blood; D010742:Phospholipid Ethers / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D011817:Rabbits; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D014230:Triazoles / Q000494:pharmacology
chemical_list: D001381:Azepines; D019007:P-Selectin; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013844:Thiazoles; D053778:Thiazolidines; D014230:Triazoles; C039351:platelet activating factor receptor; C052518:WEB 2086; C068035:4-(2-chlorophenyl)-2-(2-(4-isobutylphenyl)ethyl)-6,9-dimethyl-6H-thieno(3,2-f)(1,2,4)triazolo(4,3-a)(1,4)diazepine; C065776:3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one; C037913:CV 3988